Heart failure (HF) is among the leading causes of morbidity and mortality in many countries worldwide. Apart from Ivabradine and Cardiac Resynchronization Therapy (CRT), there have been no novel therapies for heart failure in the past years. In contrast, most drug candidates of the last decade have failed in development phase III or before.
At the same time, statin therapy has become the cornerstone treatment in primary and secondary prevention of coronary artery disease (CAD). Although CAD underlies many cases of heart failure, the use of statin therapy in chronic heart failure (CHF) is not supported by major guidelines. This is because large phase III trials of statins in CHF have been neutral. Specifically, the CORONA and the GISSI-HF trials prospectively investigated the use of rosuvastatin 10 mg daily in patients with CHF (J Am Coll Cardiol 2009; 54: 1850-9; Lancet 2008; 372: 1231-9). Both trials failed to demonstrate a beneficial effect of statin treatment on their primary end point.
The results of the CORONA and the GISSI-HF trial led to the preclusion of statin treatment in HF guidelines. However, there may be a subgroup of HF patients that could derive a benefit from statin therapy. A post-hoc analysis of the Heart Protection Study (Lancet. 2002; 360: 7-22) and the CORONA trial revealed a decreased benefit of statin treatment in patients with higher NT-proBNP levels. Similarly, statins were less beneficial in patients with high Galectin-3 levels (Eur Heart J. 2012; 33:2290-6). However, this finding about Galectin-3 and statin benefits could not be substantiated in an analysis of the GISSI-HF study (Latini R., personal communication).
Bonaca et al. 2011 (Arterioscler Thromb Vase Biol. 2011 January; 31(1):203-10) discloses a study in which it is analyzed whether GDF-15 at hospital discharge can be used as a marker for the assessment of the risk of death, recurrent myocardial infarction, and congestive heart failure. It is further analyzed whether these risks can be modified by statins. According to Bonaca, GDF-15 is not a suitable marker for therapeutic efficacy of statin treatment.
WO 09/047283 discloses a method of deciding which treatment or combination of treatments including statin treatment is to be applied in a remodeling process of a patient after a myocardial infarction which is based on the detection of three markers: natriuretic peptide, a cardiac troponin, and an inflammatory marker like GDF-15. The document, however, does not pertain to the stratification of treatment of a heart failure patient with a statin.
US 2011/0065204 discloses a method for identifying susceptibility of a patient to therapy for heart failure which is based on the quantification of GDF-15 in a sample from the patient suffering from heart failure. Statin treatment is mentioned as a possible treatment of the patients enrolled in the study described in the examples but not as a therapy for heart failure. Moreover, GDF-15 is not disclosed as a marker which can be used for identifying a patient as likely to respond to statin therapy or not.
WO 2009/138451 discloses a method of deciding which statin medication is to be applied in an apparently stable patient suffering from heart failure and undergoing a change in physiological state, the method comprising repeatedly determining, within a given time interval, an amount of the peptide markers NT-proANP, NT-proBNP, a cardiac troponin, and GDF-15 in a sample from the patient.
Sola et al. (J Card Fail. 2005 October; 11 (8):607-12) discloses that in heart failure patients treated with statins the IL-6-level decrease showing that statins exert a positive influence on inflammatory processes. The publication does not disclose that IL-6 can be used for the stratification before the therapeutic use of statins in heart failure patients.
WO 2007/26214 discloses a method of predicting patient response to a drug or drug candidate. As one of several drugs, statins are mentioned.
In the context of the studies underlying the present invention, it was advantageously shown that GDF-15 (Growth Differentiation Factor 15), Urea, SHBG (Sex Hormone-Binding Globulin), Uric acid, PLGF (Placental Growth Factor), IL-6 (Interleukin-6), Transferrin, a cardiac Troponin, sFlt-1 (Soluble fms-like tyrosine kinase-1), Prealbumin, Ferritin, Osteopontin, sST2 (soluble ST2), and hsCRP (high sensitivity C-reactive protein) can be used in order to identify subgroups of heart failure patients responding to statin therapy. In particular, biomarker levels in blood may predict whether a heart failure patient will derive a benefit or will derive harm from statin therapy.